Cribriform-morular variant of papillary thyroid carcinoma: a study of 3 cases featuring the PIK3CA mutation

The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is an unusual neoplasm with a considerably important association with familial adenomatous polyposis in young women, characterized by a peculiar histologic morphology with mixed cribriform, papillary, solid, tall columnar, and morular patterns. However, it can also occur sporadically. The molecular pathogenesis of sporadic CMV-PTC is not completely understood. We report cases of 3 patients with sporadic CMV-PTC with PIK3CA mutations. Using sequencing analyses and immunohistochemistry, we examined KRAS, BRAF, PIK3CA, and CTNNB1 mutations and related proteins, including β-catenin, PTEN, CD10, estrogen receptor, progesterone receptor, cytokeratin 19, and cyclin D1 in 3 CMV-PTCs. The 3 patients were teenaged girls. The tumors were solitary and encapsulated without cervical lymph node metastasis. They showed no recurrence for more than 6 years after the operation. Three tumors were diffusely positive for β-catenin, cyclin D1, and PTEN. The biphasic immunohistochemical patterns between the morular and nonmorular components were identified; the nonmorular components were positive for estrogen receptor, progesterone receptor, and cytokeratin 19, whereas the morular components showed CD10 positivity. All tumors harbored the same mutation in exon 9, codon 545 of the PIK3CA gene (p.E545A), whereas the KRAS, BRAF, and CTNNB1 mutations were not detected. This is the first study identifying the PIK3CA mutation specifically in sporadic CMV-PTC. The presence of the PIK3CA mutation and the wild-type KRAS, BRAF, CTNNB1 genes, and the intact PTEN expression in 3 sporadic CMV-PTCs may suggest the possible contribution of the PIK3CA mutation in its tumorigenesis.